Prostate cancer (PCA) is the second leading cause of cancer-related death in men and is expected to cause 28,170 deaths in the United States in 2012 (Siegel et al. (2012) CA Cancer J Clin 62: 10-29). PCA generally affects men over 65 years of age but remains indolent and asymptomatic in a majority of cases. The histopathological and molecular heterogeneity of the disease makes prediction of prognosis challenging. Although PSA is the most widely used serum marker for prostate cancer, it has no accepted cut-off point with high sensitivity and specificity and often leads to false positive results (Manne et al. (2005) Drug Discov Today 10: 965-976; Grizzle et al. (2004) Urol Oncol 22: 337-343; Thompson et al. (2005) JAMA 294: 66-70). Furthermore, there are currently no molecular markers that can be used to reliably predict which premalignant lesions will recur or develop into invasive PCA (Manne et al. (2005) Drug Discov Today 10: 965-976; Grizzle et al. (2004) Urol Oncol 22: 337-343; Thompson et al. (2005) JAMA 294: 66-70; Salagierski and Schalken (2012) J Urol 187: 795-801; Kristiansen (2012) Histopathology 60: 125-141). A valid biomarker should have the following characteristics: (i) accuracy (should not falsely predict positive or negative results); (ii) selectivity (ability to diagnose the disease during disease progression); and (iii) specificity (ability to distinguish cancerous from non-cancerous phenotype). Although PSA fulfills most of these criteria and is widely used, it is limited by its low values of specificity and selectivity (Manne et al. (2005) Drug Discov Today 10: 965-976; Grizzle et al. (2004) Urol Oncol 22: 337-343; Thompson et al. (2005) JAMA 294: 66-70; Salagierski and Schalken (2012) J Urol 187: 795-801; Kristiansen (2012) Histopathology 60: 125-141).
Because of the growing evidence for over-treatment of prostate cancer, it is important to identify and validate new prognostic markers that will predict clinically significant prostate cancer (Kristiansen (2012) Histopathology 60:125-141; Lopergolo and Zaffaroni (2009) Cancer 115:3058-3067; Lughezzani et al. (2010) Eur Urol 58:687-700; Fromont et al. (2012) Prostate; Garcia et al. (2006) Clin Cancer Res 12:980-988). Such markers will enable the targeted treatment of patients with aggressive tumors while avoiding unnecessary treatment and its side effects in patients with indolent disease.